Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain
Abstract Background Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to t...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02839-1 |
| _version_ | 1811334658019819520 |
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| author | Helena Port Signe Holm Nielsen Sofie Falkenløve Madsen Anne-Christine Bay-Jensen Morten Karsdal Sengül Seven Inge Juul Sørensen Lone Morsel-Carlsen Mikkel Østergaard Susanne Juhl Pedersen |
| author_facet | Helena Port Signe Holm Nielsen Sofie Falkenløve Madsen Anne-Christine Bay-Jensen Morten Karsdal Sengül Seven Inge Juul Sørensen Lone Morsel-Carlsen Mikkel Østergaard Susanne Juhl Pedersen |
| author_sort | Helena Port |
| collection | DOAJ |
| description | Abstract Background Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. Methods We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. Results Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). Conclusions Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions. |
| first_indexed | 2024-04-13T17:12:17Z |
| format | Article |
| id | doaj.art-ebd8ebad17884205955bf1c8bfadd0d3 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-13T17:12:17Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-ebd8ebad17884205955bf1c8bfadd0d32022-12-22T02:38:15ZengBMCArthritis Research & Therapy1478-63622022-06-0124111310.1186/s13075-022-02839-1Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back painHelena Port0Signe Holm Nielsen1Sofie Falkenløve Madsen2Anne-Christine Bay-Jensen3Morten Karsdal4Sengül Seven5Inge Juul Sørensen6Lone Morsel-Carlsen7Mikkel Østergaard8Susanne Juhl Pedersen9Nordic Bioscience A/S, ImmunoscienceNordic Bioscience A/S, ImmunoscienceNordic Bioscience A/S, ImmunoscienceNordic Bioscience A/S, ImmunoscienceNordic Bioscience A/S, ImmunoscienceRigshospitalet, Center for Arthritis ResearchUniversity of Copenhagen, Clinical MedicineFrederiksberg Hospital, RadiologyUniversity of Copenhagen, Clinical MedicineRigshospitalet, Center for Arthritis ResearchAbstract Background Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease, associated with extracellular matrix (ECM) remodeling of the cartilage, bone, and connective tissues. The primary symptom of axSpA is back pain, caused by inflammation. However, there is a medical need to truly identify patients with axSpA from other subjects with buttock or low back pain attributable to other reasons. We aimed to investigate circulating biomarkers of ECM/inflammation (MMP-degraded type I (C1M), II (C2M, T2CM), III (C3M), IV (C4M), VI (C6M), and X (C10C, COL10NC) collagens, CRPM, PROM and VICM) and ECM formation of type II (PRO-C2), III (PRO-C3), IV (PRO-C4), and VI (PRO-C6) collagens as potential biomarkers to identify patients with axSpA. Methods We measured biomarkers from a cross-sectional study with 204 participants by enzyme-linked immunosorbent assay (ELISA). The study included axSpA patients (N = 41), women with postpartum buttock/pelvic pain (N = 46), disc herniation (N = 25), and a group of healthy subjects (including women without postpartum pelvic pain (N = 14), subjects with various types of physical strain (cleaning staff (N = 26) long-distance runners (N = 23)), and healthy men (N = 29)). Differences between the groups were calculated by ANCOVA and AUC, while Spearman’s correlations were performed with ECM biomarkers and clinical scores. Results Patients with axSpA expressed significantly higher levels of C1M, C4M, and VICM (p < 0.05-p < 0.0001) compared to all the non-axSpA control groups. Further, C6M and PRO-C4 were significantly higher in patients with axSpA (both p < 0.0001) compared to women with postpartum pelvic pain and healthy subjects, whereas PRO-C3 was significantly lower compared to healthy subjects (p = 0.01). The best ECM common biomarker to differentiate between axSpA and the non-axSpA control groups was PRO-C4 (AUC ≥ 0.75; specificity ≥ 0.79, sensitivity = 0.65). Mild correlations were observed between collagen turnover and inflammation biomarkers and CRP and MRI (ρ ≥ 0.3; p < 0.05-p < 0.001). Conclusions Biomarkers of type I, IV, and VI collagen and biomarkers of inflammation showed an altered turnover in patients with axSpA compared with the non-axSpA control groups. Such biomarkers may be useful in combination with MRI or independently to separate patients with axSpA from other back pain conditions.https://doi.org/10.1186/s13075-022-02839-1Axial spondyloarthritisExtracellular matrixBiomarkers |
| spellingShingle | Helena Port Signe Holm Nielsen Sofie Falkenløve Madsen Anne-Christine Bay-Jensen Morten Karsdal Sengül Seven Inge Juul Sørensen Lone Morsel-Carlsen Mikkel Østergaard Susanne Juhl Pedersen Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain Arthritis Research & Therapy Axial spondyloarthritis Extracellular matrix Biomarkers |
| title | Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain |
| title_full | Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain |
| title_fullStr | Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain |
| title_full_unstemmed | Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain |
| title_short | Extracellular matrix protein turnover markers are associated with axial spondyloarthritis—a comparison with postpartum women and other non-axial spondyloarthritis controls with or without back pain |
| title_sort | extracellular matrix protein turnover markers are associated with axial spondyloarthritis a comparison with postpartum women and other non axial spondyloarthritis controls with or without back pain |
| topic | Axial spondyloarthritis Extracellular matrix Biomarkers |
| url | https://doi.org/10.1186/s13075-022-02839-1 |
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